Abstract:
:Inhibition of heat shock protein 90 (Hsp90) is known to be a significantly effective strategy in cancer therapy. Here, pyrazolopyranopyrimidine derivatives were characterized as new Hsp90 inhibitors. The molecules' key structure (ZINC02819805) was determined by utilizing a pharmacophore model virtual screening workflow. Structural optimization was then carried out on compound ZINC02819805, pyrazolopyranopyrimidine derivatives were designed and six chosen derivatives were synthesized. The inhibition of Hsp90 ATPase activity of synthesized compounds revealed that para methylphenyl derivative of pyrazolopyranopyrimidine (HM3) was the most potent inhibitor (IC50 = 5.5 µM). The anti-proliferative activity of this compound was evaluated against a panel of cell lines including MCF-7, HeLa and HUVEC (IC50 = 1.28 µM, IC50 = 1.74 µM and IC50 = 61.48 µM respectively) by MTT method. The western blot analysis of treated MCF-7 cells with compound HM3 showed that the expression level of Hsp70 and Her2 proteins changed. The high level of Hsp70 expression and low level of Her2 expression suggest that compound HM3 exhibits inhibitory effect on Hsp90. Finally, the key interactions between HM3 and Hsp90 protein were studied by molecular dynamics simulation and showed that compound HM3 was stable in Hsp90 active cite during 200 ns simulation. AbbreviationsHsp90Heat shock protein 90MTT3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromideATPadenosine triphosphateMDmolecular dynamics simulationRMSDroot-mean-square deviationRMSFroot-mean-square fluctuationRggyration radiusm-SABNPsboehmite nanoparticles-supported sulfamic acidCommunicated by Ramaswamy H. Sarma.
journal_name
J Biomol Struct Dynjournal_title
Journal of biomolecular structure & dynamicsauthors
Abbasi M,Amanlou M,Aghaei M,Bakherad M,Doosti R,Sadeghi-Aliabadi Hdoi
10.1080/07391102.2019.1660216subject
Has Abstractpub_date
2020-08-01 00:00:00pages
3462-3473issue
12eissn
0739-1102issn
1538-0254journal_volume
38pub_type
杂志文章abstract::Solvent properties of aqueous media (dipolarity/polarizability, hydrogen bond donor acidity, and hydrogen bond acceptor basicity) were measured in the coexisting phases of Dextran-PEG aqueous two-phase systems (ATPSs) containing .5 and 2.0 M urea. The differences between the electrostatic and hydrophobic properties of...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2015.1135823
更新日期:2017-01-01 00:00:00
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journal_title:Journal of biomolecular structure & dynamics
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journal_title:Journal of biomolecular structure & dynamics
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doi:10.1080/07391102.2016.1154893
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journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/073911012010525025
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journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2005.10507028
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journal_title:Journal of biomolecular structure & dynamics
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pub_type: 杂志文章
doi:10.1080/07391102.2020.1819425
更新日期:2020-09-14 00:00:00
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journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2016.1160257
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journal_title:Journal of biomolecular structure & dynamics
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doi:10.1080/073911012010525031
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pub_type: 杂志文章
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journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2005.10507032
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journal_title:Journal of biomolecular structure & dynamics
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journal_title:Journal of biomolecular structure & dynamics
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doi:10.1080/07391102.2019.1602079
更新日期:2020-03-01 00:00:00
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journal_title:Journal of biomolecular structure & dynamics
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doi:10.1080/07391102.2003.10506906
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journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.1983.10507469
更新日期:1983-12-01 00:00:00
abstract::Communicated by Ramaswamy H. Sarma. ...
journal_title:Journal of biomolecular structure & dynamics
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journal_title:Journal of biomolecular structure & dynamics
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doi:10.1080/07391102.2011.672633
更新日期:2012-01-01 00:00:00
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journal_title:Journal of biomolecular structure & dynamics
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doi:10.1080/07391102.2008.10507202
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journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
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journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
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更新日期:1997-02-01 00:00:00
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journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.1988.10506498
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journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2003.10506940
更新日期:2003-12-01 00:00:00
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journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
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journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
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abstract::Novel Coronavirus or SARS-CoV-2 has received worldwide attention due to the COVID-19 pandemic, which originated in Wuhan, China leading to thousands of deaths to date. The SARS-CoV-2 Spike glycoprotein protein is one of the main focus of COVID-19 related research as it is a structural protein that facilitates its atta...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2020.1811774
更新日期:2020-08-27 00:00:00
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journal_title:Journal of biomolecular structure & dynamics
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